Microfluid system and method for production thereof

ABSTRACT

The invention generally concerns a microfluidic system having a support body provided with a lancing member and a semi-open microchannel, for the capillary transport of a sample fluid from a receiving site to a target site. In order to obtain a higher aspect ratio the support body is coated with a build-up layer which laterally defines the microchannel in the upper region.

REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of PCT Patent Application No.PCT/EP2005/008934, filed Aug. 18, 2005 which claims priority to EuropeanPatent Application No. 04019759.2, filed Aug. 20, 2004, which are herebyincorporated by reference in their entirety.

TECHNICAL FIELD

The invention generally concerns a microfluidic system. In particular toa microfluidic body having a support body provided with a lancing memberand a semi-open microchannel.

BACKGROUND

Microfluidic systems typically allow, especially in bioanalytics, theanalysis of very small amounts of fluid. For example, such systems canbe used to analyze fluids taken in situ as capillary blood for bloodglucose determinations. In addition to the microscopic volumes(microliters and less) microfluidics are characterized by structuralelements that have smaller dimensions which allow capillary forces to beutilized. In additional, the smaller dimensions have to be implementedin so-called disposables in a manner that is cost effective and suitablefor mass production. Although such processes are known from the field ofsemi-conductor technology in the form of photochemical etching forhighly integrated systems, the materials used for this purpose canhardly be used for mechanically stressed structures due to theirbrittleness. When biocompatible materials such as steel are etched, theproblem occurs that the cross-sections of the generated channelstructures do not allow optimal liquid transport due to the isotropicloss of material.

Prior art methods of manufacturing microfluidic also include applicationof a welling agent to the surface to increase fluid transportation.However, the prior techniques are less desirable since additionalproduction steps are necessary.

Typically compatibility with a detection method for an analyte in thetransported sample is required (i.e. no effect on the measurement resultor no unacceptable falsification of the measurement result). It also hasto be biocompatible (no toxic effects whatsoever) since when samples aretaken it is not possible to rule out that parts coated with the wettingagent briefly penetrate the organism. In addition, The hydrophilizationmust have an adequate storage stability.

There are physical limitations when a wetting agent is used alonewithout a suitable geometry. Such limitations are individually or incombination due to the required transport distance, independence ofposition/gravitation and/or flow rate.

Therefore, there is a need to avoid the disadvantages that occur in theprior art and for an improved microfluidic system and a productionprocess such that structures are created for an effective transport ofsmall amounts of fluids using advantageous measures.

SUMMARY

In accordance with the first aspect of the invention, the support bodyof a microfluidic system is coated with a build-up layer which laterallydefines the microchannel at least in the upper region. The coatingallows a firmly adhering structure to be formed in a simple manner witha previously shapeless substance whereby the channel formation orheightening in the build-up layer or on the side walls thereof resultsin a liquid-conducting fluidic function which is based on an increase inthe capillarity. This means that channel cross-sections with a highaspect ratio which decisively improve the capillary action can also beformed on isotropically etchable substrates. The support body can at thesame time be designed as a lancing element for lancing the skin oralternatively can have a collecting or receiving function that isseparate from a lancing element.

In yet another aspect of the invention, the microchannel has a lowercross-sectional region that is etched into the support body and anoverlying upper cross-sectional region formed in the build-up layer. Itis also possible that the build-up layer laterally delimits themicrochannel over its entire depth and thus alone has aliquid-conducting function.

In yet another aspect of the invention, the build-up layer consists of aphotoresist. This allows microfluidic structures which have the requiredrigidity and inertness for the end use to be formed on a support in asimple manner. This can be achieved by means of the fact that thebuild-up layer is photostructured in order to form or increase theheight of the microchannel such that even complex geometries can becreated with the required accuracy. The build-up layer has a layerthickness of more than 50 μm, typically in the range of 200 to 500 μm.

Yet another aspect of the invention is that the microchannel has severalpartial cross-sections etched down into the support body by successiveetching steps starting from one surface of the support body. This alsoenables a large ratio of depth to width of the microchannel to beachieved in an isotropically etchable support material. The aspect ratioachieved by this method is longer than 0.5. The microchannel has aninner width in the range of 50 to 500 μm.

In yet another aspect of the invention, the partial cross-sections inthe support body are formed by photochemical mask etching.

In yet another aspect of the invention, capillarity of the microchannelcan also be increased by providing an undercut in the region of itslongitudinal edges that one formed by underetching.

In yet another aspect of the invention, the support body consists of anisotropically etchable material. In yet another aspect, the support bodyhas a flat shaped part made of metal such as a high-grade steel thatwill improve handling rigidity, inertness and biocompatibility of themicrofluidic system. The support body formed from a flat material has athickness of 100 to 450 μm.

In yet another aspect of the invention, the build-up layer has anadditional substance or composition which increases the hydrophilicity.In yet another aspect of the invention, the wettability of a wall of themicrochannel is increased by a chemical surface treatment.

In yet another aspect of the invention, the lancing member is formedoutside of the microchannel region by etching or punching so that thevarious structures are created by uniform processes.

In yet another aspect of the system, the microfluidic system is used totransport a sample liquid from a receiving site to a target site such asa detection region for detecting the concentration of an analyte in thesample liquid.

In yet another aspect, the process of manufacturing a system having amicrochannel is achieved by applying a photoresist layer to a supportbody to increase the height of or to form a microchannel whichtransports liquid.

In yet another aspect, the microchannel is etched into the support bodyby mask etching a first photoresist layer and, after removing the firstphotoresist layer, applying a second photoresist layer which isphotostructured in order to increase the height of the microchannel.

These and other features and advantages of the present invention will bemore fully understoof from the following detailed description of theinvention taken together with the accompanying claims. It is noted thatthe scope of the claims is definitely by the recitations therein and notby the specific discussion of the features and advantages set forth inthe present description.

BRIEF DESCRIPTION OF THE DRAWINGS

The following detailed description of the embodiments of the presentinvention can be best understood when read in conjunction with thefollowing drawings, where like structure is indicated with likereference numerals and in which:

FIG. 1 shows a sample collection element as a microfluidic system totransport a sample liquid in a perspective view.

FIGS. 2 to 4 show the system according to FIG. 1 with a differentbuild-up layer of a microchannel in cross-section.

FIGS. 5 a to f show successive process steps for increasing the heightof the channel by photostructuring the system according to FIG. 1 incross-section, and

FIGS. 6 a to k show successive process steps for deepening the channelin a view corresponding to FIG. 5.

Skilled artisans appreciate that elements in the figures are illustratedfor simplicity and clarity and have not necessarily been drawn to scale.For example, the dimensions of some of the elements in the figure may beexaggerated relative to other elements to help improve understanding ofthe embodiment(s) of the present invention.

In order that the invention may be more readily understood, reference ismade to the following examples, which are intended to illustrate theinvention, but not limit the scope thereof.

DETAILED DESCRIPTION

The following description of the preferred embodiment is merelyexemplary in nature and is in no way intended to limit the invention orits application or uses.

The microfluidic system shown in the drawing as a disposable samplecollection element 10 that enables the collection and capillarytransport of small amounts of body fluid. Referring in particular toFIG. 1, the system 10 comprises a flat support body 12, a lancing member14 formed thereon and a capillary microchannel 16 which at least incertain areas can be delimited by a build-up layer 18 of the supportbody 12.

The support body 12 as a strip-shaped flat formed part consists of steelof a thickness of about 150 to 300 μm. Its proximal end section forms aholding region 20 in order to handle it during the lancing processwhereas the lancing member 14 moulded as one piece on the distal endgenerates a small wound in the skin of the user in order to be able tocollect microscopic volumes of blood or tissue fluid.

The length of the microchannel 16 is shaped like a groove or issemi-open so that it is possible to manufacture it by photolithographyas described in the following. Liquid can be effectively taken up fromthe skin or from the skin surface at the receiving site 22 in the regionof the lancing member (lancet tip 14) via the semi-open cross-sectionwithout parts of tissue being able to completely close the entrancecross-section as is the case for conventional hollow cannulas.

Liquid is transported through the capillary channel 16 to the targetsite 24 which is at a distance from the lancing member 14 and at whichthe body fluid can be analyzed. The analysis of the body fluid can beachieved in a known manner by reflection spectroscopic orelectrochemical detection methods.

The channel cross-section can be constant or can vary over the length ofthe microchannel 16. The width of the channel is in the range of 50 to500 μm, whereas the so-called aspect ratio between depth and width islarger than 0.5 and larger than 0.8 to improve the capillarity of themicrochannel. In this connection care should be taken that anapproximately semi-circular cross-section is obtained with an aspectratio of only 0.5 when the channel 16 is isotropically etched into thesupport body 12.

As shown in FIG. 2, the semi-circular lower channel region 26 formed byisotropic etching and acting as a bottom region in the support body orsubstrate 12 can be increased in height by the build-up layer 18 whilelaterally delimiting an upper open-edged channel region 28 thusobtaining overall a higher aspect ratio and hence a better capillaryaction for liquid transport. For this purpose the build-up layer 18should have a layer thickness of more than 5 μm, and in the range of 200to 500 μm.

The build-up layer 18 is not laminated as a prefabricated body onto thesupport body 12 but is applied as a permanently adhering layer from apreviously shapeless substance. A coating material is intended for thispurpose and in particular a photoresist 30. A thick film photoresist forexample based on epoxy is suitable.

In the embodiment according to FIG. 2, the photoresist 30 is appliedsubsequently after etching the lower region 26 such that thecomplementary upper channel region 28 can additionally convey liquid.For this purpose the hydrophilicity of the layer 18 is increased bysuitable additives or by an appropriate lacquer composition. It is alsopossible to improve the water affinity of the channel walls by achemical surface treatment after structuring.

In the embodiment according to FIG. 3, the photoresist 30 used as a maskfor etching the lower region 26 on the support body 12 is not removedbut is retained for an additional fluidic function. As shown in additionto increasing the height of the channel walls it is also possible toreduce the surface 32 that is open towards the atmosphere by theundercut which further increases the capillarity. It is basically alsoconceivable to manufacture an undercut edge region of the channel 16 asan underetched structure of the support body 12 by suitable selection ofthe etching parameters.

FIG. 4 shows an embodiment in which the build-up layer 18 laterallydelimits the microchannel 16 over its entire depth wherein in this caseit is also possible to achieve a high aspect ratio by an appropriatelayer thickness of the photoresist 30. In addition to thephotostructuring of the channel 16 in the layer 18, the support body canbe structured by prior (isotropic) etching for example by etching outthe lancing member 14.

FIG. 5 illustrates a process sequence for photostructuring the channel16 on a previously etched support structure. Firstly the support body 12as a substrate is provided with a first photoresist layer 30′ (FIG. 5a,b). This is followed by a UV exposure through the photomask 32whereupon The photoresist 30′ is polymerized or hardened under thelight-permeable regions of the mask whereas the masked regions 34 arerinsed clear after exposure and development (FIG. 5 c,d). Subsequentlyan etching agent is applied to the support body 12 over the cutout 36thus generated in the layer 30′ to isotropically etch out the channelregion 26. After removing the photoresist layer 30′ (FIG. 5 f) a channelelevation 28 is formed by further photostructuring of a second thickfilm layer 30″ using mask 38 according to the already pre-etched channelcourse (FIG. 5 i). The hardened photoresist remains permanently on thesubstrate 12 as a build-up layer 18 and thus fulfills a fluidic functionfor an improved liquid transport.

In the process sequence shown in FIG. 6, the aspect ratio of the channel16 is increased by several successive etching steps. An upper partialcross-section 40 of the channel 16 is formed in the support body 12 by afirst etching according to the previous description of FIGS. 5 a to f(FIG. 6 a to f). Then a deepened partial cross-section 42 is generatedby repeating these steps at least once in a second or further etching sothat channel 16 penetrates almost the entire support body 12 withoutextending isotropically in width (FIG. 6 g to k). It is basicallypossible to carry out the etchings in parallel in opposing directionsfrom both sides of the support body 12 until the channel 16 has beencompletely etched through in which case at least the bottom side must beclosed for example by laminating on a foil.

It is noted that terms like “preferably”, “commonly”, and “typically”are not utilized herein to limit the scope of the claimed invention orto imply that certain features are critical, essential, or evenimportant to the structure or function of the claimed invention. Rather,these terms are merely intended to highlight alternative or additionalfeatures that may or may not be utilized in a particular embodiment ofthe present invention.

For the purposes of describing and defining the present invention it isnoted that the term “substantially” is utilized herein to represent heinherent degree of uncertainty that may be attributed to anyquantitative comparison, value, measurement, or other representation.The term “substantially” is also utilized herein to represent the degreeby which a quantitative representation may vary from a stated referencewithout resulting in a change in the basic function of the subjectmatter at issue.

Having described the invention in detail and by reference to specificembodiments thereof, it will be apparent that modification andvariations are possible without departing from the scope of theinvention defined in the appended claims. More specifically, althoughsome aspects of the present invention are identified herein as preferredor particularly advantageous, it is contemplated that the presentinvention is not necessarily limited to these preferred aspects of theinvention.

1. A microfluidic system for collecting body fluids, the systemComprising: a support body comprising a lancing member; a semi-openmicrochannel, located on the support body such that the microchannelassists in the capillary transport of a fluid from a receiving site to atarget site; and a build-up layer coated on the support body for thefluid transport which laterally defines the microchannel in the upperregion.
 2. The system according to claim 1, wherein the microchannel hasa lower cross-sectional region that is etched into the support body andan overlying upper cross-sectional region formed in the build-up layer.3. The system according to claim 1, wherein the build-up layer laterallydelimits the microchannel over its entire depth.
 4. The system accordingto claim 1, wherein the build-up layer consists of a thick filmphotoresist.
 5. The system according to claim 1, wherein the build-uplayer is photostructured in order to form or increase the height of themicrochannel.
 6. The system according to claim 1, wherein the build-uplayer has a layer thickness of more than 50 μm.
 7. The system accordingto claim 6, wherein the thickness of the build-up layer is 200 to 500μm.
 8. The system according to claim 1, wherein the microchannel hasseveral partial cross-sections etched down into the support body bysuccessive etching steps starting from one surface of the support body.9. The system according to claim 8, wherein the partial cross-sectionsare formed by photochemical mask etching.
 10. The system according toclaim 1, wherein a aspect ratio depth to width of the microchannel islarger than 0.5.
 11. The system according to claim 1, wherein themicrochannel has an inner width in the range of 50 to 500 μm.
 12. Thesystem according to claim 1, wherein the microchannel has an undercut inthe region of its longitudinal edges formed by underetching.
 13. Thesystem according to claim 1, wherein the support body consists of anisotropically etchable material.
 14. The system according to claim 1,wherein the support body has a flat shaped part consisting of metal. 15.The system according to claim 14, wherein the support body formed from aflat material has a thickness of 100 to 450 μm.
 16. The system accordingto claim 1, wherein the build-up layer has an additional substance orcomposition which increases the hydrophilicity.
 17. The system accordingto claim 1, wherein the wettability of a wall of the microchannel isincreased by a chemical surface treatment.
 18. The system according toclaim 1, wherein the lancing member is formed by etching or punching andis positioned outside the microchannel.
 19. A method of manufacturing amicrofluidic system to collect a body fluid, the method comprising:providing a support body having a lancing member; and applying aphotoresist layer to the support body to form a semi-open microchannelthat transports body fluid from a receiving site to a target site. 20.The method according to claim 19, wherein the photoresist is sprayed orknife coated onto the support body as a thick film or is applied by dipcoating.
 21. The method according to claim 19, wherein the process offorming the microchannel comprises the steps of: photochemically etchinga first photoresist layer; removing the first photoresist layer;applying a second photoresist layer and its photostructured in order toincrease the height of the microchannel.